dolutegravir + rilpivirine switch study (doriss)

Conditions: HIV Infection; HAART-treated; Virologically Controlled

Summary: the primary objective of the study is to evaluate the capacity of dolutegravir + rilpivirine vs. continued triple combination haart to maintain plasma hiv rna ≤ 50 copies/ml throughout 24 weeks in patients with plasma hiv rna ≤ 50 copies/ml for at least 2 years under conventional haart (2 nnrti + 3rd agent). the main secondary objectives are the following: * % of virologic success (plasma viral load ≤ 50 copies/ml) at w24 and w48 * % of patients who maintain a plasma viral load ≤ 50 copies / ml from d0 to w48 * % of virological failure defined by two consecutive plasma viral load \> 50 copies/ml * profile of genotypic resistance in case of virological failure. the trial will be conducted according to the design below, in 3 steps: * step 1: enrollment of 80 patients (40 in each arm) * step 2: enrollment on hold until w16 data from the 40 patients enrolled in the intervention arm have been analyzed. * step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/ml from d0 to w16 is significantly \> 70%, which translates in a maximum of 6 virologic failures.


Eligibility criteria:
inclusion criteria: * age ≥ 18 years * hiv-1 infection * treatment with suppressive triple haart (2 nrti + either 1 pi/r, or 1 nnrti, or ini), unchanged for \> 6 months, intra-class substitution within past 6 months is not considered as a treatment change. * plasma hiv-rna ≤ 50 copies/ml for \> 2 years * cd4 cell count \> 350/mm3 for \> 6 months * no prior virologic failure under an nnrti-containing or an insti-containing art regimen * no nnrti mutation on pre-art genotype (if no pre-art genotype available: no nnrti mutation on dna genotype at screening) among the following: k101e/p, e138a/g/k/q/r/s, v179l, y181c/i/v, y188l, h221y, m230i/l/v, l100i + k103n/s, l100i +k103r +v179d. * no mutation (either on pre-art genotype or on dna genotype at screening) among the following: t66k, g118r, v151l, s153f/y, r263k, t66k + l74m, e92q + n155h, q148r +n155h, q148h/k/r with at least one mutation of l74i or e138a/k/t or g140a/c/s * negative hbs ag * informed consent form signed by patient and investigator * a specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the dolutegravir + rilpivirine arm and will volunteer for this pk study * patient covered with health insurance * effective contraception exclusion criteria: * hiv-2 infection * dialysis or severe renal failure (creatinine clearance \< 30 ml/min) * history of decompensated liver disease * history of hiv-associated neurocognitive disorders * ast or alt \> 5 x uln * positive hbc ac and negative hbs ac * patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug * current pregnancy or breastfeeding * patient involved in another research that precludes enrolment in another trial * patient under guardianship, or deprived of liberty by a court or administrative decision.

Keywords: dolutegravir rilpivirine pi- and nrti- sparing art regimen switch study